tbuckley/cabot-search huggingface dataset:
In patients with type 2 diabetes or HF, SGLT2 inhibitors reduce gout-related outcomes
Authors: Katarzyna Nabrdalik, Gregory Y.H. Lip
Journal: Annals of Internal Medicine (2023)

Banerjee M, Pal R, Maisnam I, et al. Serum uric acid lowering and effects of sodium-glucose cotransporter-2 inhibitors on gout: a meta-analysis and meta-regression of randomized controlled trials. Diabetes Obes Metab. 2023;25:2697-2703. 37334516.
Causes and consequences of clonal hematopoiesis
Authors: Lachelle D. Weeks, Benjamin L. Ebert
Journal: Blood (2023)

Abstract Clonal hematopoiesis (CH) is described as the outsized contribution of expanded clones of hematopoietic stem and progenitor cells (HSPCs) to blood cell production. The prevalence of CH increases dramatically with age. CH can be caused by somatic mutations in individual genes or by gains and/or losses of larger chromosomal segments. CH is a premalignant state; the somatic mutations detected in CH are the initiating mutations for hematologic malignancies, and CH is a strong predictor of the development of blood cancers. Moreover, CH is associated with nonmalignant disorders and increased overall mortality. The somatic mutations that drive clonal expansion of HSPCs can alter the function of terminally differentiated blood cells, including the release of elevated levels of inflammatory cytokines. These cytokines may then contribute to a broad range of inflammatory disorders that increase in prevalence with age. Specific somatic mutations in the peripheral blood in coordination with blood count parameters can powerfully predict the development of hematologic malignancies and overall mortality in CH. In this review, we summarize the current understanding of CH nosology and origins. We provide an overview of available tools for risk stratification and discuss management strategies for patients with CH presenting to hematology clinics.
Discontinuation of anti-tumour necrosis factor alpha treatment owing to blood test abnormalities, and cost-effectiveness of alternate blood monitoring strategies
Authors: Abhishek Abhishek, Matthew D Stevenson, Georgina Nakafero, Matthew J Grainge, Ian Evans, Oras Alabas, Tim Card, Maarten W Taal, Guruprasad P Aithal, Christopher P Fox, Christian D Mallen, Danielle A van der Windt, Richard D Riley, Richard B Warren, Hywel C Williams
Journal: British Journal of Dermatology (2023)

There is no evidence base to support the use of 6-monthly monitoring blood tests for the early detection of liver, blood and renal toxicity during established anti-tumour necrosis factor alpha (TNFα) treatment.
Evolutionary “Crowdsourcing”: Alignment of Fitness Landscapes Allows for Cross-species Adaptation of a Horizontally Transferred Gene
Authors: Olivia Kosterlitz, Nathan Grassi, Bailey Werner, Ryan Seamus McGee, Eva M Top, Benjamin Kerr
Journal: Molecular Biology and Evolution (2023)

Genes that undergo horizontal gene transfer (HGT) evolve in different genomic backgrounds. Despite the ubiquity of cross-species HGT, the effects of switching hosts on gene evolution remains understudied. Here, we present a framework to examine the evolutionary consequences of host-switching and apply this framework to an antibiotic resistance gene commonly found on conjugative plasmids. Specifically, we determined the adaptive landscape of this gene for a small set of mutationally connected genotypes in 3 enteric species. We uncovered that the landscape topographies were largely aligned with minimal host-dependent mutational effects. By simulating gene evolution over the experimentally gauged landscapes, we found that the adaptive evolution of the mobile gene in one species translated to adaptation in another. By simulating gene evolution over artificial landscapes, we found that sufficient alignment between landscapes ensures such "adaptive equivalency" across species. Thus, given adequate landscape alignment within a bacterial community, vehicles of HGT such as plasmids may enable a distributed form of genetic evolution across community members, where species can "crowdsource" adaptation.
Comprehensive DNA Methylation Profiling of Medullary Thyroid Carcinoma: Molecular Classification, Potential Therapeutic Target, and Classifier System
Authors: Cenkai Shen, Xiao Shi, Duo Wen, Yuqing Zhang, Yuxin Du, Yu Zhang, Ben Ma, Haitao Tang, Min Yin, Naisi Huang, Tian Liao, Ting-Ting Zhang, Chang’e Kong, Wenjun Wei, Qinghai Ji, Yu Wang
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Medullary thyroid carcinoma (MTC) presents a distinct biological context from other thyroid cancers due to its specific cellular origin. This heterogeneous and rare tumor has a high prevalence of advanced diseases, making it crucial to address the limited therapeutic options and enhance complex clinical management. Given the high clinical accessibility of methylation information, we construct the largest MTC methylation cohort to date. Experimental Design: Seventy-eight fresh-frozen MTC samples constituted our methylation cohort. The comprehensive study process incorporated machine learning, statistical analysis, and in vitro experiments. Results: Our study pioneered the identification of a three-class clustering system for risk stratification, exhibiting pronounced epigenomic heterogeneity. The elevated overall methylation status in MTC-B, combined with the “mutual exclusivity” of hypomethylated sites displayed by MTC-A and MTC-C, distinctively characterized the MTC-specific methylation pattern. Integrating with the transcriptome, we further depicted the features of these three clusters to scrutinize biological properties. Several MTC-specific aberrant DNA methylation events were emphasized in our study. NNAT expression was found to be notably reduced in poor-prognostic MTC-C, with its promoter region overlapping with an upregulated differentially methylated region. In vitro experiments further affirmed NNAT's therapeutic potential. Moreover, we built an elastic-net logistic regression model with a relatively high AUC encompassing 68 probes, intended for future validation and systematic clinical application. Conclusions: Conducting research on diseases with low incidence poses significant challenges, and we provide a robust resource and comprehensive research framework to assist in ongoing MTC case inclusion and facilitate in-depth dissection of its molecular biological features.
In adults with HIV and low-to-moderate CV risk, pitavastatin reduced MACE over a median 5.1 y
Authors: Scott Selinger
Journal: Annals of Internal Medicine (2023)

Grinspoon SK, Fitch KV, Zanni MV, et al; REPRIEVE Investigators. Pitavastatin to prevent cardiovascular disease in HIV infection. N Engl J Med. 2023;389:687-699. 37486775.
Adaptive Designs in Implementation Science and Practice: Their Promise and the Need for Greater Understanding and Improved Communication
Authors: Amy Kilbourne, Matthew Chinman, Shari Rogal, Daniel Almirall
Journal: Annual Review of Public Health (2023)

The promise of adaptation and adaptive designs in implementation science has been hindered by the lack of clarity and precision in defining what it means to adapt, especially regarding the distinction between adaptive study designs and adaptive implementation strategies. To ensure a common language for science and practice, authors reviewed the implementation science literature and found that the term adaptive was used to describe interventions, implementation strategies, and trial designs. To provide clarity and offer recommendations for reporting and strengthening study design, we propose a taxonomy that describes fixed versus adaptive implementation strategies and implementation trial designs. To improve impact, (a) futureimplementation studies should prespecify implementation strategy core functions that in turn can be taught to and replicated by health system/community partners, (b) funders should support exploratory studies that refine and specify implementation strategies, and (c) investigators should systematically address design requirements and ethical considerations (e.g., randomization, blinding/masking) with health system/community partners.
Deleterious and Adaptive Mutations in Plant Germplasm Conserved Ex Situ
Authors: Yong-Bi Fu, Gregory W Peterson, Carolee Horbach
Journal: Molecular Biology and Evolution (2023)

Conserving more than 7 million plant germplasm accessions in 1,750 genebanks worldwide raises the hope of securing the food supply for humanity for future generations. However, there is a genetic cost for such long-term germplasm conservation, which has been largely unaccounted for before. We investigated the extent and variation of deleterious and adaptive mutations in 490 individual plants representing barley, wheat, oat, soybean, maize, rapa, and sunflower collections in a seed genebank using RNA-Seq technology. These collections were found to have a range of deleterious mutations detected from 125 (maize) to 83,695 (oat) with a mean of 13,537 and of the averaged sample-wise mutation burden per deleterious locus from 0.069 to 0.357 with a mean of 0.200. Soybean and sunflower collections showed that accessions acquired earlier had increased mutation burdens. The germplasm with more years of storage in several collections carried more deleterious and fewer adaptive mutations. The samples with more cycles of germplasm regeneration revealed fewer deleterious and more adaptive mutations. These findings are significant for understanding mutational dynamics and genetic cost in conserved germplasm and have implications for long-term germplasm management and conservation.
The Mifepristone Litigation: Untangling the Implications of the Fifth Circuit’s Decision for Abortion Access and the U.S. Food and Drug Administration
Authors: Patricia J. Zettler, Lewis A. Grossman, Eli Y. Adashi, I. Glenn Cohen
Journal: Annals of Internal Medicine (2023)

In August 2023, a federal appeals court issued an opinion in Alliance for Hippocratic Medicine v FDA, a case wherein a group of antiabortion medical organizations and physicians have challenged U.S. Food and Drug Administration (FDA) approval and regulation of mifepristone. This opinion contained some good news for the FDA, drug makers, and patients: the appeals court declined to halt the marketing of mifepristone altogether (as the trial court judge would have). But the court also decided that the FDA’s 2016 and 2021 actions expanding the indication for mifepristone, lowering the drug’s dose, and loosening restrictions on its distribution and use were likely unlawful, and it thus affirmed the trial court’s order staying these actions. In this article, we explain key aspects of the opinion to health care professionals and consider the ways in which the appeals court’s reasoning and conclusions, if followed by the Supreme Court, could undermine abortion access and public health going forward.
The Story of Ferumoxytol: Synthesis Production, Current Clinical Applications, and Therapeutic Potential
Authors: Mengmeng Long, Yan Li, Hongliang He, Ning Gu
Journal: Advanced Healthcare Materials (2023)

Ferumoxytol, approved by the U.S. Food and Drug Administration in 2009, is one of the intravenous iron oxide nanoparticles authorized for the treatment of iron deficiency in chronic kidney disease and end-stage renal disease. With its exceptional magnetic properties, catalytic activity, and immune activity, as well as good biocompatibility and safety, ferumoxytol has gained significant recognition in various biomedical diagnoses and treatments. Unlike most existing reviews on this topic, this review primarily focuses on the recent clinical and preclinical advances of ferumoxytol in disease treatment, spanning anemia, cancer, infectious inflammatory diseases, regenerative medicine application, magnetic stimulation for neural modulation, etc. Additionally, the newly discovered mechanisms associated with the biological effects of ferumoxytol are discussed, including its magnetic, catalytic, and immunomodulatory properties. Finally, the summary and future prospects concerning the treatment and application of ferumoxytol-based nanotherapeutics are presented.
Relationship Between Clinician Language and the Success of Behavioral Weight Loss Interventions
Authors: Charlotte Albury, Helena Webb, Elizabeth Stokoe, Sue Ziebland, Constantinos Koshiaris, Joseph J. Lee, Paul Aveyard
Journal: Annals of Internal Medicine (2023)

International guidelines recommend that primary care clinicians recognize obesity and offer treatment opportunistically, but there is little evidence on how clinicians can discuss weight and offer treatment in ways that are well received and effective.
Loss of p73 Expression Contributes to Chronic Obstructive Pulmonary Disease
Authors: Bradley W. Richmond, Clayton B. Marshall, Jessica B. Blackburn, Tiffany S. Tufenkjian, Brian D. Lehmann, Wei Han, Dawn Newcomb, Sergey S. Gutor, Raphael P. Hunt, Danielle L. Michell, Kasey C. Vickers, Vasiliy V. Polosukhin, Timothy S. Blackwell, Jennifer A. Pietenpol
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Multiciliated cell (MCC) loss and/or dysfunction is common in the small airways of patients with chronic obstructive pulmonary disease (COPD), but it is unclear if this contributes to COPD lung pathology.
Multiomics Analysis Provides Novel Pathways Related to Progression of Heart Failure
Authors: Wouter Ouwerkerk, Joao P. Belo Pereira, Troy Maasland, Johanna E. Emmens, Sylwia M. Figarska, Jasper Tromp, Andrea L. Koekemoer, Christopher P. Nelson, Mintu Nath, Simon P.R. Romaine, John G.F. Cleland, Faiez Zannad, Dirk J. van Veldhuisen, Chim C. Lang, Piotr Ponikowski, Gerasimos Filippatos, Stefan Anker, Marco Metra, Kenneth Dickstein, Leong L. Ng, Rudolf A. de Boer, Natal van Riel, Max Nieuwdorp, Albert K. Groen, Erik Stroes, Aeilko H. Zwinderman, Nilesh J. Samani, Carolyn S.P. Lam, Evgeni Levin, Adriaan A. Voors
Journal: Journal of the American College of Cardiology (2023)
Plasma Proteomics to Identify Drug Targets for Ischemic Heart Disease
Authors: Mohsen Mazidi, Neil Wright, Pang Yao, Christiana Kartsonaki, Iona Y. Millwood, Hannah Fry, Saredo Said, Alfred Pozarickij, Pei Pei, Yiping Chen, Daniel Avery, Huaidong Du, Dan Valle Schmidt, Ling Yang, Jun Lv, Canqing Yu, Junshi Chen, Michael Hill, Michael V. Holmes, Joanna M.M. Howson, Richard Peto, Rory Collins, Derrick A. Bennett, Robin G. Walters, Liming Li, Robert Clarke, Zhengming Chen, Junshi Chen, Zhengming Chen, Robert Clarke, Rory Collins, Liming Li, Chen Wang, Jun Lv, Richard Peto, Robin Walters, Daniel Avery, Maxim Barnard, Derrick Bennett, Ruth Boxall, Sushila Burgess, Ka Hung Chan, Yiping Chen, Zhengming Chen, Johnathan Clarke, Robert Clarke, Huaidong Du, Ahmed Edris Mohamed, Hannah Fry, Simon Gilbert, Pek Kei Im, Andri Iona, Maria Kakkoura, Christiana Kartsonaki, Hubert Lam, Kuang Lin, James Liu, Mohsen Mazidi, Iona Millwood, Sam Morris, Qunhua Nie, Alfred Pozarickij, Paul Ryder, Saredo Said, Dan Schmidt, Becky Stevens, Iain Turnbull, Robin Walters, Baihan Wang, Lin Wang, Neil Wright, Ling Yang, Xiaoming Yang, Pang Yao, Xiao Han, Can Hou, Qingmei Xia, Chao Liu, Jun Lv, None Pei, Dianjanyi Sun, Canqing Yu, Naying Chen, Duo Liu, Zhenzhu Tang, Ningyu Chen, Qilian Jiang, Jian Lan, Mingqiang Li, Yun Liu, Fanwen Meng, Jinhuai Meng, Rong Pan, Yulu Qin, Ping Wang, Sisi Wang, Liuping Wei, Liyuan Zhou, Caixia Dong, Pengfei Ge, Xiaolan Ren, Zhongxiao Li, Enke Mao, Tao Wang, Hui Zhang, Xi Zhang, Jinyan Chen, Ximin Hu, Xiaohuan Wang, Zhendong Guo, Huimei Li, Yilei Li, Min Weng, Shukuan Wu, Shichun Yan, Mingyuan Zou, Xue Zhou, Ziyan Guo, Quan Kang, Yanjie Li, Bo Yu, Qinai Xu, Liang Chang, Lei Fan, Shixian Feng, Ding Zhang, Gang Zhou, Yulian Gao, Tianyou He, Pan He, Chen Hu, Huarong Sun, Xukui Zhang, Biyun Chen, Zhongxi Fu, Yuelong Huang, Huilin Liu, Qiaohua Xu, Li Yin, Huajun Long, Xin Xu, Hao Zhang, Libo Zhang, Jian Su, Ran Tao, Ming Wu, Jie Yang, Jinyi Zhou, Yonglin Zhou, Yihe Hu, Yujie Hua, Jianrong Jin, Fang Liu, Jingchao Liu, Yan Lu, Liangcai Ma, Aiyu Tang, Jun Zhang, Liang Cheng, Ranran Du, Ruqin Gao, Feifei Li, Shanpeng Li, Yongmei Liu, Feng Ning, Zengchang Pang, Xiaohui Sun, Xiaocao Tian, Shaojie Wang, Yaoming Zhai, Hua Zhang, Wei Hou, Silu Lv, Junzheng Wang, Xiaofang Chen, Xianping Wu, Ningmei Zhang, Weiwei Zhou, Xiaofang Chen, Jianguo Li, Jiaqiu Liu, Guojin Luo, Qiang Sun, Xunfu Zhong, Weiwei Gong, Ruying Hu, Hao Wang, Meng Wang, Min Yu, Lingli Chen, Qijun Gu, Dongxia Pan, Chunmei Wang, Kaixu Xie, Xiaoyi Zhang
Journal: Journal of the American College of Cardiology (2023)

Integrated analyses of plasma proteomic and genetic markers in prospective studies can clarify the causal relevance of proteins and discover novel targets for ischemic heart disease (IHD) and other diseases.
Imaging Methods for Evaluation of Chronic Aortic Regurgitation in Adults
Authors: Lauren S. Ranard, Robert O. Bonow, Rick Nishimura, Michael J. Mack, Vinod H. Thourani, Joseph Bavaria, Patrick T. O’Gara, Jeroen J. Bax, Philipp Blanke, Victoria Delgado, Jonathon Leipsic, Roberto M. Lang, Hector I. Michelena, João L. Cavalcante, Torsten P. Vahl, Martin B. Leon, Vera H. Rigolin
Journal: Journal of the American College of Cardiology (2023)
In CAD, P2Y12 inhibitor vs. aspirin monotherapy reduces a composite CV outcome without increasing major bleeding
Authors: Manasi Tannu, L. Kristin Newby
Journal: Annals of Internal Medicine (2023)

Gragnano F, Cao D, Pirondini L, et al; PANTHER Collaboration. P2Y12 inhibitor or aspirin monotherapy for secondary prevention of coronary events. J Am Coll Cardiol. 2023;82:89-105. 37407118.
Copper Nanodots‐Based Hybrid Hydrogels with Multiple Enzyme Activities for Acute and Infected Wound Repair
Authors: Yuyu Cui, Wei Zhang, Jie Shan, Jia He, Qiang Niu, Can Zhu, Wenqi Wang, Xu‐Lin Chen, Xianwen Wang
Journal: Advanced Healthcare Materials (2023)

Effectively controlling bacterial infection, reducing the inflammation and promoting vascular regeneration are all essential strategies for wound repair. Nanozyme technology has potential applications in the treatment of infections because its non-antibiotic dependent, topical and noninvasive nature. In wound management, copper-based nanozymes have emerged as viable alternatives to antibiotics. In this study, an ultrasmall cupric enzyme with high enzymatic activity is synthesized and added to a nontoxic, self-healing, injectable cationic guar gum (CG) hydrogel network. The nanozyme exhibits remarkable antioxidant properties under neutral conditions, effectively scavenging reactive nitrogen and oxygen species (RNOS). Under acidic conditions, Cu NDs have peroxide (POD) enzyme-like activity, which allows them to eliminate hydrogen peroxides and produce free radicals locally. Antibacterial experiments show that they can kill bacteria and remove biofilms. It reveals that low concentrations of Cu ND/CG decrease the expression of the inflammatory factors in cells and tissues, effectively controlling inflammatory responses. Cu ND/CG hydrogels also inhibit HIF-1α and promote VEGF expression in the wound with the ability to promote vascular regeneration. In vivo safety assessments reveal a favorable biosafety profile. Cu ND/CG hydrogels offer a promising solution for treating acute and infected wounds, highlighting the potential of innovative nanomaterials in wound healing.
Deep Learning–Enabled Assessment of Left Heart Structure and Function Predicts Cardiovascular Outcomes
Authors: Emily S. Lau, Paolo Di Achille, Kavya Kopparapu, Carl T. Andrews, Pulkit Singh, Christopher Reeder, Mostafa Al-Alusi, Shaan Khurshid, Julian S. Haimovich, Patrick T. Ellinor, Michael H. Picard, Puneet Batra, Steven A. Lubitz, Jennifer E. Ho
Journal: Journal of the American College of Cardiology (2023)
Cognitive decline accelerated in over 50s during pandemic, study finds
Authors: Owen Dyer
Journal: BMJ (2023)

Cognitive decline accelerated in over 50s during pandemic, study finds Owen DyerThe covid-19 pandemic brought a "sustained decline in cognition" to people in the UK aged over 50, including those who did not fall sick, showed a large longitudinal study that tracked the same people before and after SARS-CoV-2 struck.
Cardiac Amyloid Detection by PET/CT Imaging of Iodine (124I) Evuzamitide (124I-p5+14)
Authors: Jonathan S. Wall, Emily B. Martin, Ronald Lands, Radhakrishnan Ramchandren, Alan Stuckey, R. Eric Heidel, Bryan Whittle, Dustin Powell, Tina Richey, Angela D. Williams, James S. Foster, Spencer Guthrie, Stephen J. Kennel
Journal: JACC. Cardiovascular imaging (2023)
The Need for Randomized Trials to Define the Optimal Dose of Anticoagulants for Atrial Fibrillation in Chronic Kidney Disease
Authors: Sean D. Pokorney, Christopher B. Granger
Journal: Circulation (2023)

ptimal drug dosing should be the dose shown to be safe and effective in randomized trials.For patients with atrial fibrillation (AF) who are similar to patients included in the ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation), the apixaban dose should be 5 mg twice daily, or 2.5 mg in those with at least 2 dosereduction criteria (age ≥80 years, weight ≤60 kg, and creatinine level ≥1.5 mg/dL).With respect to chronic kidney disease (CKD), we can be confident in the standard dosing for estimated creatinine clearance (CrCl) down to 25 mL/min, or into the stage 4 CKD population, as these patients were included in ARISTOTLE.European Medicines Agency labeling differs from that of the Food and Drug Administration and recommends 1 dose-reduction criterion (if CrCl is 15 to 29 mL/min).
Long-Term Incidence of Atrial Fibrillation in Patients With Autoimmune Disease
Authors: Guoli Sun, Ole Ahlehoff, Emil L. Fosbøl, Morten Schou, Mikkel Faurschou, Jesper Hastrup Svendsen, Lars Køber, Jawad H. Butt
Journal: Journal of the American College of Cardiology (2023)
Overall Survival With Circulating Tumor Cell Count–Driven Choice of Therapy in Advanced Breast Cancer: A Randomized Trial
Authors: François-Clément Bidard, Nicolas Kiavue, William Jacot, Thomas Bachelot, Sylvain Dureau, Hugues Bourgeois, Anthony Goncalves, Etienne Brain, Sylvain Ladoire, Florence Dalenc, Joseph Gligorov, Luis Teixeira, George Emile, Jean-Marc Ferrero, Delphine Loirat, Luc Cabel, Amir Kadi, Véronique Diéras, Catherine Alix-Panabières, Jean-Yves Pierga
Journal: Journal of Clinical Oncology (2023)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. In patients with hormone receptor–positive, human epidermal growth factor receptor 2–negative advanced breast cancer, the STIC CTC trial established that, for choosing between endocrine therapy (ET) or chemotherapy, the use of circulating tumor cell (CTC) count is noninferior to the investigator's choice in terms of progression-free survival. Here, we report overall survival (OS) results, a secondary end point. Patients were randomly assigned in a 1:1 ratio to have their first-line treatment (ET or chemotherapy) determined by investigators or CTC count (chemotherapy if ≥ 5 CTCs/7.5 mL; ET if low CTC count; CellSearch). OS was assessed at the discontinuation of follow-up. After a median follow-up of 4.7 years, 382 deaths (50.6%) had occurred among 755 patients. Median OS was 51.3 months (95% CI, 46.8 to 55.1) in the CTC arm and 45.5 months (95% CI, 40.9 to 51.1) in the standard arm (hazard ratio [HR] for death, 0.85; 95% CI, 0.69 to 1.03; P = .11). Among 189 patients (25.0%) with ET recommended by clinicians and high CTC count, chemotherapy was superior to ET (HR for death, 0.53; 95% CI, 0.36 to 0.78; P = .001). In case of a discordant estimate, OS data demonstrate the clinical utility of CTC count.